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Ann Thorac Surg 1999;68:742-749
© 1999 The Society of Thoracic Surgeons

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Alternatives To Transplantation

Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device

^a Deutsches Herzzentrum Berlin, Germany
^b Max-Delbrück Center, Berlin, Germany

Address for reprint requests to Dr Hetzer, Deutsches Herzzentrum Berlin, Augustenburger Platz #1, 13353 Berlin, Germany

Presented at the Fourth International Conference on Circulatory Support Devices for Severe Cardiac Failure, Houston, TX, Oct 3–5, 1997.

Abstract

Background. Lasting recovery from intractable end-stage dilated cardiomyopathy, which occurs with ventricular unloading, has recently been demonstrated in 5 patients. Here our extended clinical experience with the "weaning" concept is presented.

Methods. In 19 patients (23 to 65 years) with intractable end-stage dilated cardiomyopathy, ventricular assist devices were explanted after support periods of up to 26 months, when repeat off-pump studies had shown either restoration of cardiac function (left ventricular ejection fraction, > 45%) and dimensions (left ventricular internal diameter in diastole, < 55 mm) or partial recovery (left ventricular ejection fraction between 35% and 40%) with serious complications on the device. At the time of device placement left ventricular ejection fraction was below 20% and left ventricular internal diameter in diastole more than 64 mm and bridge-to-transplantation had been planned.

Results. Seven patients with persistently restored cardiac function for more than 8 months and 5 patients for less than 5 months after weaning were studied. Five patients with recurrent heart failure died within 4 to 8 months after explantation. Four patients had to be transplanted and 2 died for reasons unrelated to cardiac function. An individual optimal left ventricular ejection fraction and left ventricular internal diameter in diastole was reached before pump removal was actually conducted in all patients. These parameters gradually deteriorated until pump removal.

Conclusions. Lasting recovery can be reached by ventricular unloading in a subset of patients with intractable end-stage dilated cardiomyopathy. Obviously, there is an individual optimum of recovery that cannot be further improved by prolonged unloading.

The ever-increasing number of patients with end-stage idiopathic dilated cardiomyopathy (IDC), who are awaiting a heart transplantation, has made the use of ventricular assist devices (LVAD) a clinical routine to keep patients alive who would otherwise die before they reach the lifesaving transplantation. The time that some of these patients spend on such a mechanical device has now reached several months and even years. It has been observed by some groups of researchers that during ventricular unloading periods, grossly dilated and failing hearts displayed an astonishing size reduction and restoration of function [1–5].

Elective explantation of a LVAD (Novacor N100 PCQ) with complete recovery was first performed at our institution on March 8, 1995, in a 39-year-old man. At the time of implantation, the heart was quite enlarged with a left ventricular internal diameter in diastole (LVIDd) of 72 mm. His left heart function was remarkably impaired with a left ventricular ejection fraction (LVEF) of 15% (Fig 1).

View larger version (152K): [in this window] [in a new window]   Fig 1. Chest roentgenogram of a 39-year-old patient (No. 1) with dilated cardiomyopathy, intractable heart failure, and pulmonary edema immediately before assist implantation.

View larger version (153K): [in this window] [in a new window]   Fig 2. Chest roentgenogram of patient (No. 1) 2 days after elective ventricular assist device explantation after 160 days of support.

View larger version (143K): [in this window] [in a new window]   Fig 3. Chest roentgenogram of patient (No. 1) 2.5 years after elective ventricular assist device explantation.

Since this initial success, 19 patients with IDC, who required mechanical support, underwent device explantation. The clinical data and the courses of these 19 patients are outlined in this report.

Patients and methods

The demographic data of the 19 patients are listed in Table 1. There were 18 men and 1 woman, with ages ranging from 23 to 65 years (mean, 45.6 years). All suffered from chronic IDC with symptoms of heart failure noted between 1 and 13 years before admission. At the time of assist implantation, all were dependent on intravenous catecholamines and phosphodiesterase inhibitors with cardiac indexes ranging from 1.1 to 2.3 L · min^-1 · m^-2 (mean, 1.7 ± 0.42 L · min^-1 · m^-2) and mean pulmonary artery pressure of 18 to 45 mm Hg (mean, 34 ± 7.1 mm Hg). On echocardiography the left ventricular function was impaired (Table 2). The LVEF ranged from 10% to 20% (mean, 15.8% ± 2.6%) and the hearts were significantly dilated; the LVIDd was 64 mm at the lowest and 93 mm at the highest (mean, 76.2 ± 7.1 mm). All patients consented to device implantation as a bridge-to-transplantation. In 16 patients a N100 PCQ LVAD from Novacor (Baxter Co, Oakland, CA) was implanted. In 1 patient each a pneumatic HeartMate IP LVAD from TCI (TCI HeartMate, Woburn, MA) (patient 4), an electric vented HeartMate VE LVAD from TCI (patient 14), and a biventricular pneumatic paracorporeal pulsatile Berlin Heart with a heparin-coated inner surface (Mediport Kardiotechnik, Berlin, Germany) (patient 11) with a left atrial cannula that passed through the mitral valve into the left ventricle were implanted.

Operative procedures and devices
Implantation of the LVADs was performed according to the well-established procedures. In addition, as a routine nitrous oxide insufflation was started at a rate of 10 parts per million for discontinuation of extracorporeal circulation, which in the case of less-than-optimal right ventricular contraction was increased to 30 parts per million. In addition, triiodothyronine 20 µg was injected as a bolus, followed by a continuous infusion of 1 µg/h for 80 hours postoperatively [8]. In 1 patient (No. 11) a biventricular extracorporeal pulsatile pneumatic assist system (Berlin Heart) was applied with a left atrial transmitral-tipped cannula for left ventricular venting and end-to-side connection of the assist cannula to the right atrium, the pulmonary artery, and the ascending aorta [9]. Pump chamber volumes in this patient were 60 mL on the right side and 80 mL on the left.

The explantation procedure in LVAD patients was performed under full hemodynamic and transesophageal monitoring after the administration of 10,000 IU of heparin and after the pump was stopped for at least 20 minutes with one pump beat per 20 seconds. When cardiac function remained completely stable, the pump pocket was reentered, the graft of the outflow cannula was exposed, clamped, divided, and oversewn. Next, the drive line was cut. The mobilized pump and the inflow cannula were then approached and divided in the same fashion. The intrathoracic parts of both cannulas were left in place. In 2 patients (Nos. 3 and 4) with chronic graft infection, who had had pump pocket infection during the assist period, the remainder of the cannulas were later removed through thoracotomy. In the case of a biventricular Berlin Heart system the cannulas were removed through resternotomy under extracorporeal circulation.

Procedures during the assist period
Anticoagulation was started 24 hours after device implantation. After an initial course of heparin, the patients on Novacor and Berlin Heart systems were placed on Coumadin, aspirin, and dipyridamole and for the 2 patients on a TCI system only aspirin and dipyridamole. Among routine laboratory studies the levels of ß₁-adrenoceptor autoantibodies are determined before, during, and eventually after the assist period [7, 10, 11].

When repeated weekly echocardiographic studies revealed a size decrease of the ventricles and more vigorous contractions pump-off studies were planned. Before the pump-off studies heparin was administered, the pump was brought to a halt and the function of the heart was observed by transesophageal echocardiography for at least 10 minutes with a single stoke every 20 seconds. As soon as a fairly normalized (> 40% ejection fraction) heart function was seen during such study periods, the electrical pumps were programmed to a "fixed rate" modus to effect some afterload strain on the left ventricle. When ventricular recovery persisted over the following weeks, elective pump explantation was considered.

In the majority of patients pump explantation was scheduled when the best possible state of myocardial recovery was reached. In the other patients (Nos. 7, 14, 18, 19) pump-related complications prompted pump removal when significant improvement of heart function had occurred, but a more complete state of recovery would have been preferred. In these patients, further stabilization after pump removal was anticipated. The reasons for "premature" pump explantation were cerebral bleeding (patient 7), hemorrhage from the inflow cannula and pocket infection (patient 14), recurrent hemothorax (patient 18), and signs of mediastinal bleeding (patient 19).

Results

On weekly-performed echocardiography the size of the left ventricles shrank steadily. During off-pump studies LVIDd had reached a minimum (eg, "optimal" size after various times on assist; range, 24 to 294 days; mean, 88.7 ± 79.4 days; Table 2). By then the LVIDd had decreased to between 39 mm and 55 mm (mean, 48.8 ± 5.5 mm). At the time of pump explantation after assist periods of between 30 and 794 days (mean, 187 ± 181.8 days), reenlargement of the left ventricles had set in and LVIDd then measured between 40 and 66 mm (mean, 52.7 ± 8.2 mm).

Similarly, the originally highly impaired left ventricular function during the assist period showed a considerable improvement of contracting behavior, LVEF reached an "optimum" of between 40% and 65% (mean, 47.4% ± 5.5%) after 16 to 382 days (mean, 115 ± 94 days). Again, by the time of assist explantation LVEF showed a small redeterioration and measured 35% minimum and 55% maximum (mean, 44.3% ± 5.9%).

The majority of patients (12 of 19) have been stable with normal or near-normal cardiac function for up to 2.5 years and in 7 patients for more than 8 months. This was also the case in 5 additional patients in whom the time elapsed since pump explantation is only 1 to 3 months, which is too short for mid-term evaluation.

Two patients died after pump explantation, both from causes not attributable to heart function. One (patient 13) developed massive intrapulmonary hemorrhage of unresolved origin on the eighth postoperative day after an uneventful course with good cardiac function. The other patient (No. 7) had an excellent recovery of heart function in familial cardiomyopathy. However, after being discharged home in good condition, he was admitted to his local hospital as an emergency and died with the symptoms of massive pulmonary embolism.

Five patients (Nos. 6, 8, 11, 12, and 14) experienced a recurrence of heart failure, of whom 4 have undergone successful heart transplantation (5, 6, 7, and 7 months after assist explantation, respectively), and one patient (No. 11) is on the transplant waiting list. Patient No. 6 was the one with the longest assist application of 795 days on a Novacor system. A detailed description of his course is published elsewhere [8]. The majority of the patients with stable cardiac recovery after assist explantation showed, after adaptation to regular loading conditions, some further improvement on follow-up studies (Table 2 and Figs 4 and 5 ).

View larger version (27K): [in this window] [in a new window]   Fig 4. Courses of left ventricular internal diameter in diastole (LVIDd) mean values in the four groups. Last values in the courses indicate either the most recent follow-up data or data at time of listing for heart transplantation (HTx) or last data obtained in 2 patients who died. Statistical analysis indicates that LVIDd values in groups Ia and II were significantly different at times of "optimal recovery" and "explantation" (see Tables for group allocation).

View larger version (26K): [in this window] [in a new window]   Fig 5. Mean values of left ventricular ejection fraction (LVEF) during the courses in the four groups. Last values in the courses indicate either most recent follow-up data or data at time of listing for heart transplantation (HTx) or last data obtained in the 2 patients who died. Statistical analysis indicates that LVEF values in group Ia and II were significantly different at "time of explantation" (see Tables for group allocation).

Dilated cardiomyopathy is widely believed to be irreversible in the majority of cases. Once this type of myocardial disease has reached the clinical state of intractable heart failure, heart transplantation has been the sole treatment for this condition. Also, in our experience with more than 1,000 heart transplants since 1986, dilated cardiomyopathy has continued to be the underlying disease in more than two-thirds of the patients. Consequently, a similar proportion of patients (187) with IDC (66%) were placed on mechanical circulatory support systems within our bridge-to-transplant clientele.

Thus, it was an unexpected experience to see gradual and, finally, complete recovery of hearts, which had been grossly dilated and poorly contracting, once they were unloaded for some time by an assist device. This eventually led us to explant the assist pumps in 19 patients, who in the majority have proved to be stable for up to 2.5 years.

Two factors seem to be important for the potential of myocardial recovery to become apparent. First, the great disparity of numbers of patients waiting for heart transplantation and of available donor organs has resulted in an ever-increasing waiting time for the patients on assist devices, which unwittingly provided sufficient time for the recovery process to become visible. Second, the more recently introduced application of implantable assist devices (Novacor N100 PCQ and TCI HeartMate VE) which, with large cannula apical drainage, has afforded complete left ventricular unloading that seems to be essential for myocardial recovery. In none of the patients treated with our paracorporeal pneumatic system (Berlin Heart) with only atrial drainage was significant ventricular recovery observed, which is obviously related to insufficient ventricular drainage.

The potential for recovery under LVAD support has been assumed and discussed during recent years by some investigators, mostly from the observation of a well-functioning heart, which is removed at the time of transplantation [3, 12, 13]. In a few such instances the assist system was explanted, the obviously normalized heart was left in place, and transplantation was discontinued. However, there had been no long-lasting recovery success, which cast doubts on the validity of such a "weaning" concept. The ensuing discussion recalled some observations of earlier cardiology researchers who had treated patients with IDC by strict bed rest for many months after which time significant improvement of the hitherto failing hearts was noted [14]. The beneficial effects of chronic afterload reduction on IDC hearts by angiotensin-converting enzyme inhibitor intake may be seen in the same context of left ventricular unloading, and the current lively discussion of partial ventriculectomy (Batista and colleagues [15]) must be mentioned at this point.

The underlying process of myocardial recovery in IDC remains unclear. The hitherto unproven hypothesis relates IDC to chronic inflammation [16]. Prolonged unloading and optimal coronary perfusion, which provides a resting period for the heart, may allow a healing process to take place that was accompanied by a reduction of myocardial cytokines, a decrease of neurohumoral activity, and an up-regulation of ß-receptor density [17–19].

Our initial hesitant approach to explant the life-sustaining pump was to wait long enough to see the heart in normal function for several weeks. However, in the light of our present data, it appears that recovery, if it occurs, is reached within a few weeks. Beyond this time of "optimal recovery," a process of gradual loss of ventricular function seems to occur. It has been discussed whether this observation represents an increase of myocardial fibrosis or atrophy [20–22].

In all the patients in whom heart failure reoccurred after pump explantation, there had been a time of "optimal recovery" that had been missed by waiting longer for an even better functional status.

However, in most of the patients with recurrent failure, the time on the assist pump, until "optimal recovery" had been reached, was considerably longer than in the patients who after pump explantation enjoyed a permanently recovered heart function. One may assume that these two groups had a different myocardial condition to begin with, but if this should be the case, it was not within the scope of recognition. The two groups did not show any differences as to duration or depth of heart failure, type of heart disease, or known origin.

This leads to the most important point of the entire concept, that is, the search for parameters, biochemical or morphologic that would reliably predict the potential for complete recovery. Because of the lack of such a predictor we do not believe that it is justified to take the step toward elective assist device implantation in IDC and maintain the present emergency implantation regimen as a bridge-to-transplantation.

The observation of high autoantibody levels against ß₁-receptors before assist implantation, which invariably disappear with mechanical support, cannot serve as predictor for recovery before assist implantation. However, the antibody disappearance does seem to coincide with ventricular recovery [6]. Assuming that an out of control self-perpetuating stimulation of the ß-receptors may play an essential role in the pathophysiology of end-stage IDC, we consider an accompanying treatment with ß-blockers during the assist period, and particularly after assist explantation, highly important.

Explantation of assist pumps and leaving both the inflow and the outflow cannulas in place has not created any detectable disadvantages, except in 2 patients who had had pump pocket infections during the assist period and who continued to demonstrate chronic graft infection after pump removal. In both instances the remainder of the graft material had to be explanted by a thoracotomy at a second stage.

In conclusion of our still preliminary, although exciting experience, there seems to be a substantial proportion of patients with end-stage heart failure in IDC, in whom the hearts may have an astonishing potential for complete recovery of their myocardial function when unloaded for a certain time. Many questions remain to be answered, such as the time frame and the course of recovery, the duration of recovery that can be attained, and, most important, the characterization of those patients who may be good candidates for such a recovery and weaning treatment.

Apart from such therapy-oriented questions, the observations in this patient group, in our opinion, opens the door for reconsideration of the pathophysiology in IDC, thus prompting the need for a host of further basic scientific studies.

Finally, if the recovery of the such-treated hearts should prove to last for years, for the first time a convincing alternative to heart transplantation in this patient group may be on hand.

References

1. Holman W.L., Bourge R.C., Kirklin J.K. Case report: circulatory support for 70 days with resolution of acute heart failure. J Thorac Cardiovasc Surg 1991;102:932-934.[Medline]
2. Nakatani T., Sasako Y., Kumon K., et al. Long-term circulatory support to promote recovery from profound heart failure. ASAIO J 1995;41:M526-M530.[Medline]
3. Levin H.R., Oz M.C., Catanese K.A., Rose E.A., Burkhoff D. Transient normalisation of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy. J Heart Lung Transplant 1996;15:840-842.[Medline]
4. Levin H.R., Oz M.C., Chen J.M., Packer M., Rose E.A., Burkhoff D. Reversal of chronic ventricular dilatation in patients with end-stage cardiomyopathy by prolonged mechanical unloading. Circulation 1995;91:2717-2720.[Abstract/Free Full Text]
5. Frazier O.H., Benedect C.R., Radovancevic B., et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:675-682.[Abstract/Free Full Text]
6. Müller J., Wallukat G., Weng Y., et al. Weaning from mechanical cardiac support in patients with dilated cardiomyopathy. Circulation 1997;96:542-549.[Abstract/Free Full Text]
7. Loebe M., Weng Y., Müller J., et al. Successful mechanical circulatory support for more than two years with a left ventricular assist device in a patient with dilated cardiomyopathy. J Heart Lung Transplant 1997;16:1176-1179.[Medline]
8. Klemperer J.D., Klein I., Gomez M., et al. Thyroid hormone treatment after coronary-artery bypass surgery. N Engl J Med 1995;333:1522-1527.[Abstract/Free Full Text]
9. Schiessler A., Warnecke H., Friedel N., Hennig E., Hetzer R. Clinical use of the Berlin biventricular assist device as a bridge to transplantation. ASAIO Trans 1990;36:M706-M708.[Medline]
10. Wallukat G., Wollenberger A. Effects of serum gamma globulin fractions of patients with allergic asthma and dilated cardiomyopathy on chronotropic ß-adrenoceptor function in cultured neonatal rat heart myocytes. Biomed Biochim Acta 1987;46:634-639.
11. Wallukat G., Wollenberger A., Morwinski R., Pitschner H.F. Anti-ß₁-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy. J Mol Cell Cardiol 1995;27:397-406.[Medline]
12. Rose E.A., Frazier O.H. Resurrection after mechanical circulatory support [Editorial]. Circulation 1997;96:393-395.
13. Nakatani S., McCarthy P.M., Kottke-Marchant K., et al. Left ventricular echocardiographic and histologic changes. J Am Coll Cardiol 1996;27:894-901.[Abstract]
14. Burch G.E. On resting the human heart. Am Heart J 1966;71:422.[Medline]
15. Batista R.J., Santos J.L., Takeshita N., Bocchino L., Lima P.N., Cunha M.A. Partial left ventriculectomy to improve left ventricular function in end-stage heart disease. J Card Surg 1996;11:96-98.[Medline]
16. Caforio A.L., Stewart J.T., Bonifacio E., et al. Inappropriate major histocompatibility complex expression on cardiac tissue in dilated cardiomyopathy. Autoimmunity 1990;83:515-522.
17. Hummel M., Czerlinski S., Friedel N., et al. Interleukin-6 and interleukin-8 concentrations as predictors of outcome in ventricular assist device patients before heart transplantation. Crit Care Med 1994;22:448-454.[Medline]
18. Hosenpud J.D., Campbell S.M., Mendelson D.J. Interleukin-1 induced myocardial depression in an isolated perfused beating heart preparation. J Heart Transplant 1989;8:460-464.[Medline]
19. Altemose G.T., Gritsus V., Jeevanandam V., Goldman B., Margulies K.B. Altered myocardial phenotype after mechanical support in human beings with advanced cardiomyopathy. J Heart Lung Transplant 1997;16:765-773.[Medline]
20. Tomantek R.J., Cooper G. Morphological changes in the mechanically unloaded myocardial cell. Anat Rec 1981;200:271-280.[Medline]
21. Scheinin S.A., Capek P., Radovancevic B., Duncan J.M., McAllister H.A., Frazier O.H. The effect of prolonged left ventricular support on myocardial histopathology in patients with end-stage cardiomyopathy. ASAIO J 1992;38:M271-M274.[Medline]
22. Kinoshita M., Takano H., Takaichi S., Taenaka Y., Nakatani T. Influence of prolonged ventricular assistance on myocardial histopathology in intact heart. Ann Thorac Surg 1996;61:640-645.[Abstract/Free Full Text]

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				H. T. Tevaearai, A. D. Eckhart, G. B. Walton, J. R. Keys, K. Wilson, and W. J. Koch Myocardial Gene Transfer and Overexpression of {beta}2-Adrenergic Receptors Potentiates the Functional Recovery of Unloaded Failing Hearts Circulation, July 2, 2002; 106(1): 124 - 129. [Abstract] [Full Text] [PDF]

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				N. de Jonge, D. F. van Wichen, M. E. I. Schipper, J. R. Lahpor, F. H. J. Gmelig-Meyling, E. O. Robles de Medina, and R. A. de Weger Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading: An immunohistochemical analysis of the contractile myofilaments J. Am. Coll. Cardiol., March 20, 2002; 39(6): 963 - 969. [Abstract] [Full Text] [PDF]

				R. Sodian, M. Loebe, C. Schmitt, E. V. Potapov, H. Siniawski, J. Muller, H. Hausmann, H. R. Zurbruegg, Y. Weng, and R. Hetzer Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1942 - 1949. [Abstract] [Full Text] [PDF]

				O. H. Frazier, E. A. Rose, M. C. Oz, W. Dembitsky, P. McCarthy, B. Radovancevic, V. L. Poirier, and K. A. Dasse Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation J. Thorac. Cardiovasc. Surg., December 1, 2001; 122(6): 1186 - 1195. [Abstract] [Full Text] [PDF]

				J. D. Madigan, A. Barbone, A. F. Choudhri, D. L. S. Morales, B. Cai, M. C. Oz, and D. Burkhoff Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 902 - 908. [Abstract] [Full Text] [PDF]

				M.H. Yacoub A novel strategy to maximize the efficacy of left ventricular assist devices as a bridge to recovery Eur. Heart J., April 1, 2001; 22(7): 534 - 540. [PDF]

				A. Y. Schure, P. C. Laussen, and F. X. McGowan JR Mechanical Cardiopulmonary Support of Infants and Children With Congenital Heart Disease Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2001; 5(1): 46 - 54. [Abstract] [PDF]

				M. A. Acker Mechanical circulatory support for patients with acute-fulminant myocarditis Ann. Thorac. Surg., March 1, 2001; 71 (2007): S73 - S76. [Abstract] [Full Text] [PDF]

				G. S. Kumpati, P. M. McCarthy, and K. J. Hoercher Left ventricular assist device bridge to recovery: a review of the current status Ann. Thorac. Surg., March 1, 2001; 71 (2007): S103 - S108. [Abstract] [Full Text] [PDF]

				R. Hetzer, J. H. Muller, Y.-g. Weng, R. Meyer, and M. Dandel Bridging-to-recovery Ann. Thorac. Surg., March 1, 2001; 71 (2007): S109 - S113. [Abstract] [Full Text] [PDF]

				L. W. Stevenson and R. L. Kormos Mechanical cardiac support 2000: current applications and future trial design: June 15-16, 2000 Bethesda, Maryland J. Am. Coll. Cardiol., January 1, 2001; 37(1): 340 - 370. [Full Text] [PDF]